Sensitivity analyses from the INPULSIS™ trials of nintedanib

Background: Nintedanib, an intracellular inhibitor of tyrosine kinases, is in development for the treatment of idiopathic pulmonary fibrosis (IPF). The INPULSIS™ trials were two replicate, 52-week, randomized, double-blind, placebo-controlled Phase III trials that investigated the efficacy and safety of nintedanib 150 mg twice daily in 1066 patients with IPF. The primary endpoint was the annual rate of decline in forced vital capacity (FVC). Key secondary endpoints were time to first acute exacerbation over 52 weeks and change from baseline in St. George's Respiratory Questionnaire (SGRQ) total score over 52 weeks.

Aim: Sensitivity analyses were conducted to test the robustness of the results of the primary and key secondary endpoints in the INPULSIS™ trials.

Methods: Pre-specified sensitivity analyses tested model assumptions and sensitivity to data handling, including handling of missing data, in each trial.

Results: In both trials, sensitivity analyses were all consistent with the primary analysis of the annual rate of decline in FVC, confirming superiority of nintedanib versus placebo. Sensitivity analyses for the key secondary endpoints were consistent with the primary analyses in each trial. All treatment effect estimates were very close to estimates of the primary analyses, confirming a significantly reduced risk of acute exacerbation and a significantly smaller increase in SGRQ total score (indicating less deterioration in health-related quality of life) in the nintedanib group versus placebo in INPULSIS™-2 and no significant difference between groups in INPULSIS™-1.

Conclusion: In the INPULSIS™ trials, the robustness of the primary and key secondary endpoint results was supported by sensitivity analyses.

Presented at ERS 2014